This study investigated associations between chronic medical conditions, activities of daily living (ADL), and health-related quality of life (HRQOL). Our findings suggest that the number of ADL limitations reported by older adults is associated with their HRQOL. Findings from our analyses also suggest that the association between having multiple comorbid conditions and HRQOL is stronger for those with no ADL limitations than those with at least some limitations. These data will aid practitioners in determining the relative importance of chronic medical conditions and ADL limitations on HRQOL and demonstrate how ADL limitations and comorbid conditions may differentially impact HRQOL.